Clinical efficacy of CO2 fractional laser in treating post‐burn hypertrophic scars in children: A meta‐analysis

Abstract Objective To evaluate and explore the efficacy of CO2 fractional laser in treating post‐burn hypertrophic scars in children through Meta‐analysis. Methods English databases (PubMed, Web of Science and The National Library of Medicine), as well as Chinese databases (China National Knowledge Infrastructure and Wanfang Data) were searched. RevMan 5.3 software was used to data analysis. Results A total of 10 pieces of literature were included, involving 413 children. Meta‐analysis showed that: (1) The average Vancouver Scar Scale after surgery was significantly lower than that before surgery [weight mean difference (WMD) = −3.56, 95% confidence interval (CI):−4.53,−2.58, p < 0.001]; (2) After CO2 fractional laser, pigmentation [WMD = −0.74, 95% CI:−1.10,−0.38, p < 0.001], pliability [WMD = −0.92, 95% CI:−1.20,−0.65, p < 0.001], vascularity [WMD = −0.77, 95% CI:−1.09,−0.46, p < 0.001], height [WMD = −0.57, 95% CI:−0.95,−0.19, p < 0.001] were improved compared with those before surgery. (3) The average Visual Analogue Scale (VAS) after surgery was significantly lower than that before surgery [WMD = −3.94, 95% CI:−5.69,−2.22, p < 0.001]. (4) Both Patient and Observer Scar Assessment Scale (POSAS)‐Observer [WMD = −3.98, 95% CI:−8.44,0.47, p < 0.001] and POSAS‐Patient [WMD = −4.98, 95% CI:−8.09,−1.87, p < 0.001] were significantly lower than those before surgery. (5) Erythema and vesicles were the most common complications after CO2 fractional laser therapy, with an incidence of 4.09%. Conclusion CO2 fractional laser is beneficial to the recovery of hypertrophic scar after burn in children, and can effectively improve the scar symptoms and signs in children, with desirable clinical efficacy.

Hypertrophic scars (HS) are often secondary to burns, surgeries, lacerations, and so forth.The wounds after deep second-degree burns reach deep into the dermis and require a long time to heal, resulting in a 50%−83% incidence of HS.In addition to exposing patients to varying degrees of pain, itching, dysfunction, and so forth, scars can also seriously affect their physical and mental health, [1][2] especially for children in the growth and development stage.Recently, there have been an increasing number of burn cases in children, which has seriously affected their psychological and physiological growth and development. 3It remains a challenge regarding the prevention and treatment of HS in burn patients.Traditional methods are unlikely to achieve the desired therapeutic effect, which is due to the unwillingness of children to cooperate with anti-scar treatment, and the inability to maintain continuous pressure when applying pressure therapy in special parts of the treatment.
In the traditional treatment methods for scars, children have shown poorer compliance than adults during scar treatment methods.They are unwilling to actively cooperate with anti-scar treatment, resulting in the inability to maintain sustained pressure on scars in joint areas.Therefore, traditional therapies have limited efficacy in treating HS in children. 4 But all this has been revolutionized, a new scar treatment method that is, widely favored by doctors and scholars.
6][7] Laser technology has been used in clinical applications for decades since the 1980s.Currently, various lasers such as fractional CO 2 laser (CO 2 fractional laser, CO 2 FL) and pulsed dye laser are available for scar treatment. 8There are differences in the efficacy of various lasers on scars.Many studies in recent years have revealed the role of CO 2 fractional laser in wound repair, inhibiting excessive scar growth, and relieving pain and itching caused by scars. 9-10Huang et al. 11 showed that CO 2 fractional laser can effectively treat HS and reduce pruritus caused by scars.Miletta et al. 12 showed that, based on the theory of photothermal decomposition, a CO 2 fractional laser with a wavelength of 10600 nm has achieved different degrees of efficacy in the treatment of scars.Tan et al. 13 who used CO 2 fractional laser to treat 221 patients with post-burn HS and found that it can effectively improve the redness, swelling and hardness of scars.Some studies have also reported on the efficacy of using CO 2 fractional laser to treat post-burn scars in larger areas and in younger children with varying degrees of severity.However, there are still inconsistencies in the research results.This study aimed to systematically collect relevant literature and conduct a meta-analysis to explore the clinical effect of CO 2 fractional laser in treating post-burn HS in children.

Literature screening and data extraction
Two investigators independently screened the literature.Initial screening was performed according to the title and abstract, and then secondary screening was performed by reading the full text according to the inclusion and exclusion criteria.The opinions of a third investigator were solicited and discussed to reach a consensus when there was disagreement.Data were extracted independently by two investigators.

Literature quality evaluation
The finally included cohort studies or retrospective studies were evaluated for quality in three aspects: selection, comparability, and exposure or outcome using the Newcastle-Ottawa Scale (NOS).A total of 9 points were set in this scale, and 1 point was scored if the scoring conditions were met.Low-quality studies: scores <5, and high-quality studies: scores ≥5.Studies with a NOS score <5 were not included. 15e quality of literature was assessed with reference to the Jadad Scale.Literature with a score ≥3 was considered to meet the inclusion criteria, and literature with a score <3 was considered to be of low quality 16 and was not included.Literature that met the inclusion criteria was classified and assessed.

F I G U R E 1
Flow chart of literature screening.

Statistical analysis
Revman5.3 software was used to meta-analysis.The measurement data used the weight mean difference (WMD), while the count data used the relative risk as the effect indicator.Effect sizes were expressed as point estimates and 95% confidence intervals (CIs).
For the heterogeneity test, I 2 test was used to judge the degree of heterogeneity, with I 2 < 50% or p > 0.1 indicating the homogeneity of the included literature, which was analyzed using the fixed effects model (Mantel-Haenszel).I 2 > 50% or p≤0.1 indicated certain heterogeneity, which was analyzed using the random effects model (DerSimonian-Laird).The test level: α = 0.05.

Literature search results
A total of 945 literature was retrieved through database retrieval, of which 75 replication studies as well as 345 systematic reviews, case reports and other studies were excluded.Studies without clear diagnostic criteria and no comparative data before and after treatment were excluded, and 10 pieces of literature were finally included for Meta-analysis [17][18][19][20][21][22][23][24][25][26] (Figure 1).

Basic characteristics and quality assessment of the included literature
The 10 pieces of finally included literature were published from 2016 to 2023.The included literature involved a total of 425 children.The literature quality evaluation scores of the included retrospective studies and prospective cohort studies were between 6 and 8, both of which were medium-high quality studies; The scores of the other two randomized controlled studies were both >3, which met the inclusion criteria.The basic characteristics and quality assessment results of the included literature are detailed in Table 1.

2.3
Meta-analysis results

VSS
Preoperative and postoperative data of VSS were reported in a total of eight pieces of literature.There was heterogeneity among the studies ( I 2 = 96.6%)by meta-analysis, so a random effects model was used, as shown in Figure 2. The results showed that the average VSS after surgery was lower than that before surgery [WMD = −  [WMD = −0.57,95% CI:−0.95,−0.19,p < 0.001] were improved compared with those before surgery, with statistically significant differences.

VAS
Preoperative and postoperative data of VAS were reported in a total of two pieces of literature.There was heterogeneity among the studies ( I 2 = 97.9%)by meta-analysis, so a random effects model was used, as shown in Figure 4.The results showed that the average VAS after surgery was lower than that before surgery [WMD = −3.94,95% CI:−5.69,−2.22,p < 0.001].

POSAS
Postoperative and postoperative data on POSAS-Observer and POSAS-Patient were reported in a total of four pieces of literature.

Complications
The results of postoperative complications are shown in Table 2.The incidence of postoperative complications or adverse reactions was reported in a total of five pieces of literature.Among them, the most common postoperative complications were erythema and vesicle, with an incidence rate of 4.09%, followed by corrode, with an incidence rate of 3.51%.The incidence rates of discoloration, overgrowth and effusion of blood were all 2.34%.There were other rare complications, including wound infection and pigmentation, with an incidence of 1.17%.

DISCUSSION
In this study, based on the 10 pieces of included literature, this analysis showed that CO 2 fractional laser improved the appearance and morphology of post-burn HS in children through the preoperative and postoperative scales of VSS and POSAS.Moreover, CO 2 fractional laser significantly relieved the degree of itch, as assessed by preoperative and postoperative VAS scales.CO 2 fractional laser rarely causes complications, with damage being mild and tolerated.Most of the literature reported that complications and adverse reactions were greatly improved after CO 2 fractional laser therapy 19,23,24 It was shown that after CO 2 fractional laser therapy, the VSS score of post-burn HS in children was significantly improved compared with that before surgery, which was consistent with the conclusions of a previous meta-analysis.Peng et al. reported that included 20 pieces of literature and reported the clinical efficacy and safety of CO 2 fractional laser.CO 2 dot matrix laser treatment improved the VSS score.
They found that CO 2 fractional laser improved the VSS score.However, there is still s single study that puts forward inconsistent views.Douglas et al. found that the VSS score after CO 2 fractional laser therapy was not significantly different from that before surgery. 27The reason may be that the evaluation of VSS is subjective, and scars may be evaluated by different therapists due to the generally lengthy time span of treatment, thus having a greater impact on the results. 28,29In addition, it is worth mentioning that the dose of laser therapy was not standardized in the literature included in this study.Currently, there are very few quantitative studies in the available literature that refer to laser treatment, and most of the studies determine the dose of treatment based on the subjective judgment of the treating physician, which allows for variations in the effectiveness of laser treatment.A recent study 30 showed that the degree of temperature rise and thermal damage after laser treatment of hyperplastic scarring was directly related to the laser dose in terms of laser energy density, pulse width, and spot diameter, suggesting that this may be one of the reasons for the different conclusions in different studies.
In the present study, complications and adverse reactions of post-burn hyperplastic scars in children treated by CO 2 fractional laser were summarized and analyzed.The most common postoperative complications were erythema and vesicle, while rare complications included wound infection and pigmentation.
Recently, there have been an increasing number of burn cases in children, which has seriously affected their psychological and physiological growth and development.It remains a challenge in burn patients.Traditional methods are unlikely to achieve the desired therapeutic effect, which is due to the unwillingness of children to cooperate with antiscar treatment, and the inability to maintain continuous pressure when applying pressure therapy in special parts of the treatment.To this end, it is urgent to find a new therapy.This study is a meta-analysis evaluating the efficacy of CO 2 fractional laser therapy for HS after lower limb burns in children, demonstrating that this therapy achieves good clinical efficacy, which is worthy of clinical promotion.

Note: 1 =F I G U R E 3 F I G U R E 4
Vancouver Scar Scale (VSS); 2 = Visual Analogue Scale(VAS); 3 = The Patient and Observer Scar Assessment Scale(POSAS); 4 = Adverse reactions.F I G U R E 2 Forest plot of VSS differences.VSS, Vancouver Scar Scale.Forest plot of pigmentation, pliability, height, vascularity differences.Forest plot of VAS differences.VAS, Visual Analogue Scale.

Literature inclusion and exclusion criteria
indicators and unable to provide valid data; (3) literature without comparison data before and after treatment; (4) reviews, conference documents, expert speeches, and so forth;(5)animal experiments, repeated studies, case studies.
Basic characteristics and quality assessment grades of the included literature.
31I G U R E 5 Forest plot of patient and Observer Scar Assessment Scale differences.TA B L E 2areas.Therefore, traditional therapies have limited efficacy in treating HS in children.In contrast, CO 2 fractional laser therapy treats HS primarily through focal photothermal action.During therapy, "rectangular" microthermal damage zones can be created, each of which will form micropores at a certain depth on the skin surface.The heat from31As shown in this Meta-analysis, the POSAS-Observer and POSAS-Patient scores with post-burn HS in children after CO 2 fractional laser therapy were lower than those before therapy.This shows that the vascular distribution, flexibility, surface area, scar thickness, pigmentation